Dg

Following the smart, interesting, educating, funny and even sarcastic tweets on many subjects but read no evil, speak no evil and hear no evil

[Dg @dror66]

@MadCowCapital @CloisterRes catching the escaped MAPK signaling without adding a toxic burden that forces the patient to discontinue treatmen

[Dg @dror66]

@MadCowCapital @CloisterRes Physicians won't choose between Dax and atebimetinib in a vacuum. Instead, the future of oncology is moving toward a Dax + Atebimetinib combo.Dax will do the heavy lifting upstream, dampening RAS, PI3K, and Ral.Atebimetinib will act as a cyclic safety net downstream,

[Dg @dror66]

@MadCowCapital @CloisterRes Physicians won't choose between Dax and atebimetinib in a vacuum. Instead, the future of oncology is moving toward a Dax + Atebimetinib combo.Dax will do the heavy lifting upstream, dampening RAS, PI3K, and Ral.Atebimetinib will act as a cyclic safety net downstream, catching the

[Dg @dror66]

@MadCowCapital @CloisterRes tolerate a maximum-potency dose of dax. If the RAS inhibition is even slightly "leaky," the residual signaling is often enough to keep the tumor growing.

[Dg @dror66]

@MadCowCapital @CloisterRes in reality, it doesn't work permanently for two reasons:The "Leaky Faucet" Problem: To completely shut down PI3K and Ral signaling, you have to dose a drug high enough to achieve 100% target occupancy, 24 hours a day. Because of human toxicity constraints, patients cannot always

[Master Sea🌊 @Master_SeaSeo]

3/3 Neurosurgeons confirm CED delivery works even with minimal striatal volume left.

Eligibility expands from 17.6% to 36.9% (+2x TAM). With Sham surgery waived and robust 3-yr peer-reviewed data, AMT-130’s commercial and M&A foundation is substantially strengthened. $QURE #HD

[Master Sea🌊 @Master_SeaSeo]

2/3 MIT Press data proves geometric properties of caudate/putamen track HD progression better than simple volumetry.

Direct CED delivery into striatum halts local tissue deformation and silences toxic Exon-1 fragments where systemic therapies fail. $QURE

[Master Sea🌊 @Master_SeaSeo]

1/3 Dr. Victor Sung’s peer-reviewed paper highlights:

Global HD patients decline 0.5–0.7 pts/yr (1.5–2.1 in 3 yrs). AMT-130 patients showed <0.5 pts TOTAL decline over 3 years.

$QURE cleared the highest bar by comparing against the slowest-progressing control cohort (~0.5/yr).

[Christina D @Christina4HD]

@VPrasadMDMPH, calling United States senators “dumb” is incredibly disrespectful to the people who serve our government and to the legislative process itself.

So much hubris!

I listened to your comments, and I feel compelled to respond.

I am a daughter, a niece, a granddaughter, and someone who lives with the reality that Huntington’s disease could affect me. More than 200,000 Americans are at risk of Huntington’s disease. Behind that number are families like mine.

My dad has Huntington’s disease. My aunt has Huntington’s disease. My grandmother died from it.

Huntington’s disease is destroying my family, and I live with the reality that it could one day destroy my future, too.

So when you suggest that the push for Huntington’s disease therapies is being driven by pharma or lobbyists, I need you to understand who you are talking about.

We are patients. We are families. We are caregivers. We are people who have watched this disease take our loved ones from us.

We have every right to meet with legislators, write letters, sign petitions, and demand that our voices be heard.

And it is deeply dismissive to suggest that families advocating for a potential treatment are somehow being manipulated by industry.

While serving as CBER director, you spoke to reporters on the condition of anonymity about an investigational Huntington’s disease therapy that was under active FDA review. You characterized the treatment as a “failed therapy,” and you were subsequently identified as that official.

The Huntington’s disease community responded by mobilizing.

Nearly 50,000 people signed petitions urging the FDA to preserve a path forward for this potentially disease-modifying therapy.

Those signatures weren’t generated by a pharmaceutical company.

They came from people like me.

People who know exactly what Huntington’s disease looks like.

Now, in this podcast, you have once again publicly dismissed a therapy that has shown significant slowing of disease progression in clinical data, results the Huntington’s disease community has waited decades to see.

There is a profound difference between scrutinizing the science and publicly disparaging an ongoing Huntington’s disease clinical trial, especially when patients and families are living every day with the consequences of this disease.

And when you joke about “snake oil,” remember this:

Huntington’s disease is the snake.

I watched my grandmother die from it.

I am watching my dad live with its devastating effects.

I am watching my aunt live with its devastating effects.

And I live with the reality that it could one day come for me, and my family.

So if something you call “snake oil” ultimately proves capable of slowing this disease, yes, we are going to fight with all our might for the opportunity to have it fairly evaluated.

Not because we are naïve.

Not because pharma told us what to believe.

Not because a lobbyist told us what to say.

Because we live with Huntington’s disease.

And when you talk about a $1.4–$4 million price tag, I think the economic question needs to be much bigger:

How much does Huntington’s disease cost this country when we do nothing?

What is the value of keeping someone independent for additional years?

Keeping them working?

Keeping their spouse or caregiver in the workforce?

Delaying institutionalization?

Reducing hospitalizations, long-term care, and the enormous unpaid burden placed on American families?

A therapy that meaningfully delays disability could have an economic benefit far beyond the cost of the therapy itself.

We aren’t asking to lower the scientific bar.

We’re asking you to remember who that bar is supposed to serve.

The patients.

The families.

The caregivers.

And the future generations who deserve a chance at a different outcome.

Huntington’s disease is the snake. We are simply fighting for the chance to stop it.

[mike @mike98572986]

$qure $clpt

Q&A from Sung

He said that Uniqure actually made the numbers harder than they needed to. He felt the .5 was too low as a comparator, basically saying the results are even better. Said they wanted to make sure there is no doubt that this actually works. This is very interesting to me.

Sung does not think there should be a sham for amt 130, uses dbs as an example since they never did one.

He doesn’t know what the fda will do. He thinks they will not need one if he had to guess. The benefit he is seeing is pretty big.

[mike @mike98572986]

$qure $clpt

The Sung has spoken. Victor Sung spoke this morning. This is what he said.

Sounds like 3 year peer reviewed paper is getting released tomorrow.

They have the 10 sham patients from enroll hd database, they are trying to get them to be able to release that data. They have it. This would be amazing

Regarding stratal volume , neurosurgeons say even if a little is left, they believe they can deliver the drug.

Sung said he believes the majority of damage is happening in the striatum

8/10 patients after 1 year were no longer qualified for the trial due to volume loss.

@DesertDweller93 @peter_mantas @biggercapital

[kickoff @Trollkickoff]

🚨🗣️ 🇪🇸 Carles Puyol on what happened when he stopped his teammates from dancing after scoring against Rayo Vallecano:

“For me, it was simply common sense. I am not against dancing after a goal.”

“But it depends on the moment. We were winning 6–0 against a team that had just been relegated, at their home ground.”

“They had said before the match, ‘If I score, you and I will do this dance.’ Tiago scored and started dancing with Dani.”

“I stopped them because I felt it was not appropriate at that moment, considering how difficult the situation was for Rayo, their team and their fans.”

“It was better to show a little more calm and restraint.”

[נדב איל Nadav Eyal @Nadav_Eyal]

כמה מילים על קולגה.
בסוף השבוע שעבר שידר אורן נהרי את תוכניתו האחרונה ברשת ב'. הוא הסביר למאזינים כי מחלת ניוון השרירים (ALS) מתקדמת אצלו במהירות, ולא תאפשר לו בתוך זמן קצר להמשיך במשימת ההגשה. הוא הגיש את ההסבר והפרידה בדרכו האופיינית: מדויקת, מכובדת ומכבדת, מביטה נכוחה. אתמול בבוקר, כמה ימים מאוחר יותר, הוא נפטר.

נהרי קיבל בשבוע האחרון הררי שבחים על עשרות שנות עבודתו ברשות השידור וכאן 11. לעיתים נדירות אפשר לכתוב על אדם: כל המחמאות מוצדקות. על נהרי אפשר, ועוד איך אפשר.

אני חש צורך להוסיף על כך. כעורך חדשות חוץ, שימשתי כמקבילו כאשר עבדתי בערוץ 10, שהפך ל-13. הוא היה הוותיק שבחבורה המצומצמת של כתבי ומגישי חדשות החוץ; אני הייתי לא כ"כ צעיר, אבל הצעיר שביניהם. התכתבנו אחרי שהתגלתה מחלתו, שיחה של אנשי חדשות חוץ: שלחתי מחקרים על תרופות ניסיוניות. זה היה מאוחר מידי.

קשים חייו של כתב חוץ בישראל. מעגלי החדשות המזרח תיכוניים עמוסים בדרמה של חיינו. מלחמה ושלום, ובעיקר מלחמה. שוב ושוב יצעד עורך חדשות החוץ - מושג ארכאי שמתאר את הכתב הבכיר לעניינים בין-לאומיים - אל עורך מהדורת החדשות. הוא יסביר שמשבר המשכנתאות האמריקאי עתיד לסחוף את העולם, וגם את ישראל; שהווירוס בסין יכתיב את גורל העולם לעתיד הקרוב, שהמלחמה באוקראינה עדיין חשובה ומעניינת, גם שלוש שנים אחרי שפרצה; שיש איזה מטבע וירטואלי שנקרא ביטקוין, ושווה לדבר עליו. העורך יביט בו במבט מבין, מלא אמפטיה או קוצר רוח; "אין לנו מקום היום", הוא יפלוט. גם מחר ספק אם יהיה.

אנשים כמו אורן נהרי, ערד ניר בחדשות 12, ספי הנדלר בשעתו בהארץ, ניצן הורוביץ בערוץ 10, איתי אנגל ב"עובדה" וגם אני הקטן, מנסים וניסו להוציא את הציבור הישראלי ממעגל שוטה של חדשות מקומיות, בלבד. להצביע אל האופק ולומר: יש עולם, אנחנו חלק ממנו. אסור לנו לחשוב שישראל פועלת בחלל עצמאי לגמרי; אסור להתמכר לפרובינציאליות. נהרי, באיפוק רב, בהגינות סקרנית וסקרנות הגונה, תרם לכך תרומה עצומה.

ראוי לא רק להזכיר את עבודתו המצוינת, אלא גם להקשיב היטב לדברים שאמר @OrenNahari . "תמיד ניסיתי לכבד אתכם כקהל שראוי לעומק, לא רק לכותרות. עשיתי את זה בכתבות, תוכניות, מאמרים, הרצאות, בספרים שכתבתי. אם הצלחתי, ולו במעט, להרחיב את המבט שלכם מעבר לגבולות המדינה הקטנה שלנו ומעבר להווה – עשיתי את עבודתי", הוא אמר בתוכנית הסיום שלו, "זכרו, העולם רחב, מורכב, צריך להסתכל בו בעיניים פקוחות".

כאשר מביטים היום בחברה הישראלית, מבינים עד כמה המסר של אורן נהרי ז"ל נחוץ; ההבנה שיש עולם, שצריך ללמוד אותו, דגש על המילה "צריך" - ולעשות זאת בפיכחון גמור, תוך כדי היצמדות לעובדות, לרציונל. אילו רק קצת מהמסר הזה היה נקלט אצל אנשים רבים יותר, ישראל הייתה במקום אחר.

[Tim @Tim_Corr]

The potential increase in TAM for AMT-130 if striatum size is not a limiting factor is significant. The presentation $QURE made "CHDI - 2026 HD Therapeutics Conference – AMT-130: Propensity Score Adjustment Mitigates Potential Bias from Striatal Volume Absence in Enroll-HD" makes the case that clinical eligibility would have more than doubled if you ignored the volume criterion:

[DesertDweller_ROAR_4_A_CURE_4_HD @DesertDweller93]

While we sit around this weekend speculating on why $QURE isn't trading significantly higher than where it was back in Oct 2025, let's not lose sight of the unbelievable potential of @uniQure_NV AMT130 revenue opportunity. None of us can definitively state what the final pricing will be in terms of gross vs net revenue to QURE, but we can use other gene therapies as a guide.

Below are tables showing a low net revenue assumption of $1.5 million vs a more aggressive assumption of $2.5 million per treatment. The tables also show what a slow adoption rate compared to more aggressive adoption rates have on the revenue opportunities.

Remember, there are 40,000 people in the US who have been currently diagnosed with another 100,000 who have it who have yet to be diagnosed. These numbers will probably prove to be conservative and the rest of the world more than doubles these amounts. With that market opportunity, the number of patients needed to be treated will be in the thousands per year.

Analyst price targets are nowhere near accurate. The most aggressive peak revenue assumption I have seen uses peak revenue of about $2.5 billion which translates into about 1,000 patients being treated annually. This is ridiculously low no matter what assumptions are baked in.

When I previously tweeted similar tables, some of the push back was I was being too optimistic in the net revenue assumption. As you will see, it doesn't matter if you use $1.5 million or $2.5 million as the per treatment net revenue to QURE, the valuation comes out far greater than where we are now or where we ever got to previously with an ATH of $82.

These tables also only show revenue opportunities for AMT130 for HD and also could be generated in US alone. What happens if during the 1st half of 2027 uniQure demonstrates good to great efficacy in TLE which has a much larger patient population? These revenue projections could double or more. Management knows what they have and what the value of it is even if WS doesn't have a clue YET.

In the coming weeks (at most) we will be getting news of BLA filings in the US & UK followed by updated 3-year data and new 4-year data. Those events should ignite the uniQure rocket. These events are KNOWN and yet the street is pricing it like they don't know what is about to happen. Informed investors should not follow the crowd.

For some background. I was in Seattle Genetics for about a decade before it was bought out by Pfizer. At the time of the buyout, SGEN was generating a bit over $2 billion in annual revenue. The valuation model used as justification for this buyout projected 2030 revenue of $10 billion and they paid 4X what they were projecting revenue to be 7 years later since the buyout happened in 2023. They paid $42 billion for a company generating only $2 billion/year at the time. Let that sink in, 4X revenue based on estimates in 7 years. There are many other similar examples out there.

What the QURE buyout will be is anyone's guess but these table demonstrate what the real price targets should be based on, not the sell side analyst figures. Who knows what they actually believe because they never give all the details and assumptions behind their targets. Those targets are worthless imo.

Use your own research to determine what a fair price of uniQure is and make your buy and sell decisions accordingly based on your personal situation and risk tolerance.

My assumptions: My personal belief is that the net revenue to uniQure will be in the $2.0-2.5 million range and ultimately, at least 5,000 patients will be treated annually. I believe the revenue multiple will be somewhere in the 3-5 times range of an agreed revenue model. I understand this may be a very optimistic scenario for investors but put yourself in the patients' standpoint. There are no other options available and the ones in the clinical trials have yet to demonstrate any real LT efficacy. The demand will be off the charts.

Buyout will not be based on the most optimistic assumptions but will be the starting point in terms of what management will be shooting for and it will settle on something less. Below you can pick whatever assumption you feel is reasonable and base your targets accordingly. My target price for uniQure is in the hundreds/share within the next 3-12 months depending on how aggressive buyers will be.

Good luck to all.

[Dg @dror66]

@Bar_ShemUr "הבחירות האלה יהיו על השבעה באוקטובר ולא על שום דבר אחר" ? באמת ? הפיכה משפטית ? הפיכתה של ישראל מדמוקרטיה לדיקטטורה? הרס בתי המשפט ושלטון החוק? מאות אלפים ברחובות עוד לפני אוקטובר. כל הכבוד ליאיר גולן. החלטה מוצדקת ואמיצה

[ClearPath @ClearPath100]

$QURE FDA just approved Replimune’s RP1 as Tudriqev. This is the best datapoint for uniQure bulls all year.

The approved label rests on 91 evaluable patients, single arm, 24.2% ORR, no randomized control.

What QURE brings is a randomized sham-controlled Phase 1/2, three year durability, a propensity matched external control from Enroll-HD, and CSF NfL reduction as a supportive neurodegeneration biomarker. RMAT, Breakthrough, Fast Track.

Same review center (CBER/OTP), same accelerated approval pathway, same acting leadership that just put its name on the RP1 approval.

The mechanism is clean. One dose of AAV5 delivered by MRI guided convection enhanced infusion directly into the striatum, where a miRNA payload silences mutant huntingtin at the source.

[Lauren Holder @laurencurehd]

Yesterday, I had the opportunity to meet with @FDA_KyleD and others with the @US_FDA, and I just want to say thank you. Thank you for taking the time to listen, to ask questions, and to engage in meaningful discussion about the lived experience of Huntington's disease and the realities our community faces every day.

These conversations matter. They help build understanding, strengthen collaboration, and ensure that the patient voice remains an important part of the regulatory process. We don't expect everyone to have all the answers, but we deeply appreciate those who are willing to listen, learn, and work alongside us.

I also appreciate the acknowledgment of something our community lives with every day: Our sense of urgency. Huntington's disease does not pause, and neither does its progression. Every day matters to the families living with this disease. I am grateful that our urgency was heard and that it continues to be part of the conversation as we work together toward safe and effective treatments.

To everyone at the FDA who participated yesterday, thank you for your time, your openness, and your commitment to continuing the conversation. I am looking forward to what we can accomplish together as we continue working toward safe and effective treatments for the Huntington's disease community.

Thank you for giving our community a seat at the table. Time matters, and we are grateful our voices - and our urgency - were heard. #TimeMatters #RareDisease #Huntingtonsdisease